The Berlin Patient

The Berlin patient is a phrase that has been used on two distinct and unrelated occasions to describe a person who has received a functional cure for HIV/AIDS in Berlin, Germany. The first Berlin patient, who was discovered to not have been cured, was described in 1998.^[1] After receiving an experimental therapy, the patient, who has remained anonymous, has maintained low levels of HIV and has remained off antiretroviral therapy.^[2][3] The first patient is no longer considered to be cured of HIV and the lower levels of HIV detectable in his blood are likely because he has the HLA B*57 allele associated HIV replication control.^[4] The world renowned "second" Berlin patient, Timothy Ray Brown, was first described in 2008 following a poster presented at the CROI 2008 Conference in Boston by Dr. Gero Hütter.^[5] He received a stem cell transplant from a donor naturally resistant to HIV and has remained off antiretroviral therapy since the first day of his stem cell transplant. Timothy Ray Brown is thought to be the first and only person in the world cured of HIV.^[6][7]

Anonymous: the 1998 Berlin patient

The first Berlin patient was a German in his mid-twenties.^[3] He was a patient of Dr. Heiko Jessen in Berlin, Germany.^[1][3] He was diagnosed with acute HIV infection in 1995.^[1] He was prescribed an unusual combination therapy: didanosine, indinavir and hydroxyurea.^[3] Hydroxyurea was the most unusual of the three, as it is a cancer drug not approved by the U.S. Food and Drug Administration (FDA) for HIV treatment.^[8] The combination was part of a small trial Dr. Jessen was testing in patients during acute HIV infection.^[1] After several treatment interruptions, the patient went off the prescribed therapy completely.^[3] The virus became almost undetectable.^[3] The patient has remained off antiretroviral therapy.^[3] In 2014 a follow-up report in NEJM suggest that the patient most likely controlled HIV because of the genetic background and not because of the particular treatment he received during acute HIV infection.^[2] He is no longer considered to be cured of HIV because he has a detectable viral load likely controlled by the genetic mutation he has.^[4]

Timothy Ray Brown: the 2008 cured Berlin patient

The most famous Berlin patient is Timothy Ray Brown. He is originally from Seattle, Washington.^[9] He was diagnosed with HIV in 1995 and began antiretroviral therapy. In 2006, Timothy was diagnosed with acute myeloid leukemia (AML). His physician, Dr. Gero Hütter, at Charité Hospital in Berlin, arranged for him to receive a hematopoietic stem cell transplant from a donor with the "delta 32" mutation on the CCR5 receptor.^[10] This mutation, found at relatively high frequencies in Northern Europeans (16%), results in a mutated CCR5 protein.^[11] The majority of HIV cannot enter a human cell without a functional CCR5 gene. An exception to this is a small minority of viruses that use alternate receptors, such as CXCR4 or CCR2.^[12] Those individuals who are homozygous for the CCR5 mutation are resistant to HIV and rarely progress to AIDS. Timothy received two stem cell transplants from one donor homozygous for the delta32 mutation: one in 2007 and one in 2008.^[10] Timothy stopped taking his antretroviral medication on the day of his first transplant. Three months after the first stem cell transplant, levels of HIV rapidly plummeted to undetectable levels while his CD4 T cell count increased. In addition, blood and tissue samples from areas of the body where HIV is known to hide were tested. The results were published in the New England Journal of Medicine.^[10] Today, Timothy still remains off antiretroviral therapy and is considered cured.^[13][14][15] Today leading HIV cure scientists agree that Timothy has what is called a sterilizing cure as opposed to a functional cure. In 2012, Timothy Ray Brown announced the formation of an organization whose sole purpose is to find a cure for AIDS called the Cure for AIDS Coalition. The first project of the Cure for AIDS Coalition is the Cure Report launched on October 16, 2014 during the NIH Strategies for an HIV Cure meeting held in the Washington, DC area.^[16]

Cure Research studies inspired by Timothy Ray Brown, the Berlin Patient

Scientists around the world agree that all cure for HIV related research studies today was inspired by the remarkable case of Timothy Ray Brown, the Berlin Patient. In fact, on December 2, 2013, President Obama announced during a speech commemorating World AIDS Day; "Today I’m pleased to announce a new initiative at the National Institutes of Health to advance research into an HIV cure. We’re going to redirect $100 million into this project to develop a new generation of therapies. Because the United States should be at the forefront of new discoveries into how to put HIV into long-term remission without requiring lifelong therapies -- or, better yet, eliminate it completely."^[17] Some of the HIV cure research today inspired by the case of Timothy Ray Brown focus on gene therapy and early treatment,^[18][19][20] HIV eradication and early therapy.^[21][22]

See also

• Mississippi baby

References